scholarly journals Racial Differences in DNA Methylation-Based Age Acceleration in Preeclamptic and Normotensive Pregnancy

2020 ◽  
Author(s):  
Lacey W. Heinsberg ◽  
Mitali Ray ◽  
Yvette P. Conley ◽  
James M. Roberts ◽  
Arun Jeyabalan ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Racial Disparities ◽  
Small Sample ◽  
Cellular Aging ◽  
Neonatal Outcomes ◽  
Chronological Age ◽  
Biological Aging ◽  
Cell Type ◽  
Increased Risk ◽  
Dna Methylation Age

ABSTRACTBackgroundPreeclampsia is a leading cause of maternal and neonatal morbidity and mortality. Chronological age and race are associated with increased risk of preeclampsia; however, the pathophysiology of preeclampsia and how these risk factors impact its development, are not entirely understood. This gap precludes clinical interventions to prevent preeclampsia occurrence or to address stark racial disparities in maternal and neonatal outcomes. Of note, cellular aging rates can differ between individuals and chronological age is often a poor surrogate of biological age. DNA methylation age provides a marker of biological aging, and those with a DNA methylation age greater than their chronological age have ‘age acceleration’. Examining age acceleration in the context of preeclampsia status, and race, could strengthen our understanding of preeclampsia pathophysiology, inform future interventions to improve maternal/neonatal outcomes, and provide insight to racial disparities across pregnancy.ObjectivesThe purpose of this exploratory study was to examine associations between age acceleration, preeclampsia status, and race across pregnancy.Study designThis was a longitudinal, observational, case-control study of 56 pregnant individuals who developed preeclampsia (n=28) or were normotensive controls (n=28). Peripheral blood samples were collected at trimester-specific time points and genome-wide DNA methylation data were generated using the Infinium MethylationEPIC Beadchip. DNA methylation age was estimated using the Elastic Net ‘Improved Precision’ clock and age acceleration was computed as Δage, the difference between DNA methylation age and chronological age. DNA methylation age was compared with chronological age using scatterplots and Pearson correlations, while considering preeclampsia status and race. The relationships between preeclampsia status, race, and Δage were formally tested using multiple linear regression, while adjusting for pre-pregnancy body mass index, chronological age, and (chronological age)2. Regressions were performed both with and without consideration of cell-type heterogeneity.ResultsWe observed strong correlations between chronological age and DNA methylation age in all trimesters, ranging from R=0.91-0.95 in cases and R=0.86-0.90 in controls. We observed significantly stronger correlations between chronological age and DNA methylation age in White versus Black participants ranging from R=0.89-0.98 in White participants and R=0.77-0.83 in Black participants. We observed no association between Δage and preeclampsia status within trimesters. However, even while controlling for covariates, Δage was higher in trimester 1 in participants with higher pre-pregnancy BMI (β=0.12, 95% CI=0.02 to 0.22, p=0.02) and lower in Black participants relative to White participants in trimesters 2 (β=−2.68, 95% CI=−4.43 to −0.94, p=0.003) and 3 (β=−2.10, 95% CI=−4.03 to −0.17, p=0.03). When controlling for cell-type heterogeneity, the observations with BMI in trimester 1 and race in trimester 2 persisted.ConclusionsWe report no association between Δage and preeclampsia status, although there were associations with pre-pregnancy BMI and race. In particular, our findings in a small sample demonstrate the need for additional studies to not only investigate the complex pathophysiology of preeclampsia, but also the relationship between race and biological aging, which could provide further insight into racial disparities in pregnancy and birth. Future efforts to confirm these findings in larger samples, including exploration and applications of other epigenetic clocks, is needed.

scholarly journals A Systematic Review and Meta-analysis of Environmental, Lifestyle, and Health Factors Associated With DNA Methylation Age

2019 ◽  
Vol 75 (3) ◽  
pp. 481-494 ◽  
Author(s):  
Joanne Ryan ◽  
Jo Wrigglesworth ◽  
Jun Loong ◽  
Peter D Fransquet ◽  
Robyn L Woods
Keyword(s):  
Dna Methylation ◽  
Meta Analysis ◽  
Conclusive Evidence ◽  
Chronological Age ◽  
Biological Aging ◽  
Robust Estimate ◽  
Healthy Life ◽  
Age Related ◽  
Health Factors ◽  
Dna Methylation Age

Abstract DNA methylation (DNAm) algorithms of biological age provide a robust estimate of an individual’s chronological age and can predict their risk of age-related disease and mortality. This study reviewed the evidence that environmental, lifestyle and health factors are associated with the Horvath and Hannum epigenetic clocks. A systematic search identified 61 studies. Chronological age was correlated with DNAm age in blood (median .83, range .13–.99). In a meta-analysis body mass index (BMI) was associated with increased DNAm age (Hannum β: 0.07, 95% CI 0.04 to 0.10; Horvath β: 0.06, 95% CI 0.02 to 0.10), but there was no association with smoking (Hannum β: 0.12, 95% CI −0.50 to 0.73; Horvath β:0.18, 95% CI −0.10 to 0.46). DNAm age was positively associated with frailty (three studies, n = 3,093), and education was negatively associated with the Hannum estimate of DNAm age specifically (four studies, n = 13,955). For most other exposures, findings were too inconsistent to draw conclusions. In conclusion, BMI was positively associated with biological aging measured using DNAm, with some evidence that frailty also increased aging. More research is needed to provide conclusive evidence regarding other exposures. This field of research has the potential to provide further insights into how to promote slower biological aging and ultimately prolong healthy life.

scholarly journals Posttraumatic psychopathology and the pace of the epigenetic clock: a longitudinal investigation

2018 ◽  
Vol 49 (5) ◽  
pp. 791-800 ◽  
Author(s):  
Erika J. Wolf ◽  
Mark W. Logue ◽  
Filomene G. Morrison ◽  
Elizabeth S. Wilcox ◽  
Annjanette Stone ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Alcohol Use ◽  
Psychiatric Symptoms ◽  
Alcohol Use Disorders ◽  
Cellular Aging ◽  
Epigenetic Clock ◽  
Afghanistan War ◽  
Genome Wide ◽  
Dna Methylation Age ◽  
Over Time

AbstractBackgroundPosttraumatic stress disorder (PTSD) and stress/trauma exposure are cross-sectionally associated with advanced DNA methylation age relative to chronological age. However, longitudinal inquiry and examination of associations between advanced DNA methylation age and a broader range of psychiatric disorders is lacking. The aim of this study was to examine if PTSD, depression, generalized anxiety, and alcohol-use disorders predicted acceleration of DNA methylation age over time (i.e. an increasing pace, or rate of advancement, of the epigenetic clock).MethodsGenome-wide DNA methylation and a comprehensive set of psychiatric symptoms and diagnoses were assessed in 179 Iraq/Afghanistan war veterans who completed two assessments over the course of approximately 2 years. Two DNA methylation age indices (Horvath and Hannum), each a weighted index of an array of genome-wide DNA methylation probes, were quantified. The pace of the epigenetic clock was operationalized as change in DNA methylation age as a function of time between assessments.ResultsAnalyses revealed that alcohol-use disorders (p = 0.001) and PTSD avoidance and numbing symptoms (p = 0.02) at Time 1 were associated with an increasing pace of the epigenetic clock over time, per the Horvath (but not the Hannum) index of cellular aging.ConclusionsThis is the first study to suggest that posttraumatic psychopathology is longitudinally associated with a quickened pace of the epigenetic clock. Results raise the possibility that accelerated cellular aging is a common biological consequence of stress-related psychopathology, which carries implications for identifying mechanisms of stress-related cellular aging and developing interventions to slow its pace.

Rate of teenage pregnancy in Jordan and its impact on maternal and neonatal outcomes

2017 ◽  
Vol 31 (6) ◽  
Author(s):  
Yousef S. Khader ◽  
Anwar Batieha ◽  
Rana Kareem Al fursan ◽  
Rami Al-Hader ◽  
Sa’ad S. Hijazi
Keyword(s):  
Teenage Pregnancy ◽  
Small Sample ◽  
Adverse Outcomes ◽  
Neonatal Outcomes ◽  
National Study ◽  
Premature Delivery ◽  
Discharge Data ◽  
Increased Risk ◽  
Maternity Hospitals ◽  
Maternal And Neonatal Outcomes

Abstract Objective Research regarding the adverse outcomes of adolescent childbearing has suffered from many limitations such as a small sample size and non-representative samples. This study was conducted to determine the rate of teenage pregnancy among Jordanian adolescents and its associated adverse maternal and neonatal outcomes. Methods The study is a part of a comprehensive national study of perinatal mortality that was conducted between 2011 and 2012 in Jordan. All women who gave birth after 20 weeks of gestation in 18 maternity hospitals in Jordan between 2011 and 2012 were invited to participate in the study. Consenting women were interviewed by the trained midwives in these hospitals using a structured questionnaire prepared for the purpose of this study. Additional information was also collected based on the physical examination by the midwife and the obstetrician at admission and at discharge. Data on the newborn were also collected by the pediatric nurses and the neonatologists in these hospitals. Results The overall rate of teenage pregnancy [95% confidence interval (CI) was 6.2% (5.9%, 6.5%)]. Of the studied maternal and neonatal outcomes, women aged <20 years were more likely to deliver prematurely compared to women aged 20–35 years [odds ratio (OR)=1.5, 95% CI: 1.2, 1.9; p < 0.005)]. However, the two groups of women did not differ significantly in low birth weight delivery (OR = 1.2, 95% CI: 0.9, 1.5; p = 0.167) and neonatal mortality (OR = 1.2, 95% CI: 0.8, 1.3; p = 0.491) in the multivariate analysis. Conclusion Teenage pregnancy was associated with increased risk of premature delivery, apart from the effects of socioeconomic factors.

scholarly journals Schizophrenia is characterized by age- and sex-specific effects on epigenetic aging

2019 ◽  
Author(s):  
Anil P.S. Ori ◽  
Loes M. Olde Loohuis ◽  
Jerry Guintivano ◽  
Eilis Hannon ◽  
Emma Dempster ◽  
...  
Keyword(s):  
Accelerated Aging ◽  
Disease Status ◽  
Risk Scores ◽  
Chronological Age ◽  
Biological Aging ◽  
Disease Trajectory ◽  
Clinical Biomarkers ◽  
Age Related ◽  
Epigenetic Aging ◽  
Increased Risk

AbstractSchizophrenia (SCZ) is a severe mental illness that is associated with an increased prevalence of age-related disability and morbidity compared to the general population. An accelerated aging process has therefore been hypothesized as a component of the SCZ disease trajectory. Here, we investigated differential aging using three DNA methylation (DNAm) clocks (i.e. Hannum, Horvath, Levine) in a multi-cohort SCZ whole blood sample consisting of 1,100 SCZ cases and 1,200 controls. It is known that all three DNAm clocks are highly predictive of chronological age and capture different features of biological aging. We found that blood-based DNAm aging is significantly altered in SCZ with age- and sexspecific effects that differ between clocks and map to distinct chronological age windows. Most notably, the predicted phenotypic age (Levine clock) in female cases, starting at age 36 and beyond, is 3.21 years older compared to matching control subjects (95% CI: 1.92-4.50, P=1.3e-06) explaining 7.7% of the variance in disease status. Female cases with high SCZ polygenic risk scores present the highest age acceleration in this age group with +7.03 years (95% CI: 3.87-10.18, P=1.7E-05). Since increased phenotypic age is associated with increased risk of all-cause mortality, our findings suggests that specific and identifiable patient groups are at increased mortality risk as measured by the Levine clock. These results provide new biological insights into the aging landscape of SCZ with age- and sexspecific effects and warrant further investigations into the potential of DNAm clocks as clinical biomarkers that may help with disease management in schizophrenia.

scholarly journals Epigenetic Marker of Telomeric Age is Associated with Exacerbations and Hospitalizations in Chronic Obstructive Pulmonary Disease

2021 ◽  
Author(s):  
Ana I Hernández Cordero ◽  
Chen Xi Yang ◽  
Xuan Li ◽  
Stephen Milne ◽  
Virginia Chen ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Dna Methylation ◽  
Health Status ◽  
Pulmonary Disease ◽  
Cox Proportional Hazards Model ◽  
Chronological Age ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Age Related ◽  
Increased Risk

Abstract Background: Chronic obstructive pulmonary disease (COPD) is an age-related condition that has been associated with early telomere attrition; the clinical implications of telomere shortening in COPD are not well known. In this study we aimed to determine the relationship of the epigenetic regulation of telomeric length in peripheral blood with the risk of exacerbations and hospitalization in patients with COPD. Methods: Blood DNA methylation profiles were obtained from 292 patients with COPD enrolled in the placebo arm of the Macrolide Azithromycin to Prevent Rapid Worsening of Symptoms Associated With Chronic Obstructive Pulmonary Disease study (MACRO) and who were followed for 1-year. We calculated telomere length based on DNA methylation markers (DNAmTL) and related this biomarker to the risk of exacerbation and hospitalization and health status (St. George respiratory questionary score [SGRQ]) over this time using a Cox proportional hazards model. We also used linear models to investigate the associations of DNAmTL with the rates of exacerbations and hospitalizations (adjusted for chronological age, lung function, race, sex, smoking, and body mass index).Results: Participants with short DNAmTL demonstrated increased risk of exacerbation (P=0.02) and hospitalization (P=0.03) compared to those with longer DNAmTL. DNAmTL age acceleration was associated with higher rates of exacerbation (P=1.35x10-04) and hospitalization (P=5.21x10-03) and poor health status (SGRQ) independent of chronological age (P=0.03).Conclusion: Telomeric age based on blood DNA methylation is associated with COPD exacerbation and hospitalization and thus is a promising biomarker for poor outcomes in COPD.

scholarly journals Associations of Plasma Folate and Vitamin B6 With Blood DNA Methylation Age: An Analysis of One-Carbon Metabolites in the VA Normative Aging Study

2020 ◽  
Author(s):  
Jamaji C Nwanaji-Enwerem ◽  
Elena Colicino ◽  
Xu Gao ◽  
Cuicui Wang ◽  
Pantel Vokonas ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Vitamin B6 ◽  
Regression Models ◽  
Biological Aging ◽  
Kernel Machine ◽  
Normative Aging Study ◽  
Kernel Machine Regression ◽  
Aging Study ◽  
Dna Methylation Age ◽  
Normative Aging

Abstract One-carbon metabolism is an important contributor to aging-related diseases; nevertheless, relationships of one-carbon metabolites with novel DNA methylation-based measures of biological aging remain poorly characterized. We examined relationships of one-carbon metabolites with 3 DNA methylation-based measures of biological aging: DNAmAge, GrimAge, and PhenoAge. We measured plasma levels of 4 common one-carbon metabolites (vitamin B6, vitamin B12, folate, and homocysteine) in 715 VA Normative Aging Study participants with at least 1 visit between 1999 and 2008 (observations = 1153). DNA methylation age metrics were calculated using the HumanMethylation450 BeadChip. We utilized Bayesian Kernel Machine Regression models adjusted for chronological age, lifestyle factors, age-related diseases, and study visits to determine metabolites important to the aging outcomes. Bayesian Kernel Machine Regression models allowed for the estimation of the relationships of single metabolites and the cumulative metabolite mixture with methylation age. Log vitamin B6 was selected as important to PhenoAge (β = −1.62 years, 95% CI: −2.28, −0.96). Log folate was selected as important to GrimAge (β = 0.75 years, 95% CI: 0.41, 1.09) and PhenoAge (β = 1.62 years, 95% CI: 0.95, 2.29). Compared to a model where each metabolite in the mixture is set to its 50th percentile, the log cumulative mixture with each metabolite at its 30th (β = −0.13 years, 95% CI: −0.26, −0.005) and 40th percentile (β = −0.06 years, 95% CI: −0.11, −0.005) was associated with decreased GrimAge. Our results provide novel characterizations of the relationships between one-carbon metabolites and DNA methylation age in a human population study. Further research is required to confirm these findings and establish their generalizability.

scholarly journals Determination of saliva epigenetic age in infancy, and its association with parental socio-economic characteristics and pregnancy outcomes

2020 ◽  
pp. 1-9
Author(s):  
Maja Popovic ◽  
Valentina Fiano ◽  
Elena Isaevska ◽  
Chiara Moccia ◽  
Morena Trevisan ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Linear Regression ◽  
Pregnancy Outcomes ◽  
Positive Association ◽  
Absolute Difference ◽  
Chronological Age ◽  
Linear Regression Models ◽  
Epigenetic Age ◽  
Epigenetic Age Acceleration ◽  
Dna Methylation Age

Abstract Epigenetic age acceleration (AA) has been associated with adverse environmental exposures and many chronic conditions. We estimated, in the NINFEA birth cohort, infant saliva epigenetic age, and investigated whether parental socio-economic position (SEP) and pregnancy outcomes are associated with infant epigenetic AA. A total of 139 saliva samples collected at on average 10.8 (range 7–17) months were used to estimate Horvath’s DNA methylation age. Epigenetic AA was defined as the residual from a linear regression of epigenetic age on chronological age. Linear regression models were used to test the associations of parental SEP and pregnancy outcomes with saliva epigenetic AA. A moderate positive association was found between DNA methylation age and chronological age, with the median absolute difference of 6.8 months (standard deviation [SD] 3.9). The evidence of the association between the indicators of low SEP and epigenetic AA was weak; infants born to unemployed mothers or with low education had on average 1 month higher epigenetic age than infants of mothers with high education and employment (coefficient 0.78 months, 95% confidence intervals [CIs]: −0.79 to 2.34 for low/medium education; 0.96, 95% CI: −1.81 to 3.73 for unemployment). There was no evidence for association of gestational age, birthweight or caesarean section with infant epigenetic AA. Using the Horvath’s method, DNA methylation age can be fairly accurately predicted from saliva samples already in the first months of life. This study did not reveal clear associations between either pregnancy outcomes or parental socio-economic characteristics and infant saliva epigenetic AA.

scholarly journals Recalibrating the epigenetic clock: implications for assessing biological age in the human cortex

Brain ◽  
2020 ◽  
Author(s):  
Gemma L Shireby ◽  
Jonathan P Davies ◽  
Paul T Francis ◽  
Joe Burrage ◽  
Emma M Walker ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Age Distribution ◽  
Biological Age ◽  
Supervised Machine Learning ◽  
Tissue Type ◽  
Chronological Age ◽  
Epigenetic Clock ◽  
Methylation Data ◽  
Human Cortex ◽  
Dna Methylation Age

Abstract Human DNA methylation data have been used to develop biomarkers of ageing, referred to as ‘epigenetic clocks’, which have been widely used to identify differences between chronological age and biological age in health and disease including neurodegeneration, dementia and other brain phenotypes. Existing DNA methylation clocks have been shown to be highly accurate in blood but are less precise when used in older samples or in tissue types not included in training the model, including brain. We aimed to develop a novel epigenetic clock that performs optimally in human cortex tissue and has the potential to identify phenotypes associated with biological ageing in the brain. We generated an extensive dataset of human cortex DNA methylation data spanning the life course (n = 1397, ages = 1 to 108 years). This dataset was split into ‘training’ and ‘testing’ samples (training: n = 1047; testing: n = 350). DNA methylation age estimators were derived using a transformed version of chronological age on DNA methylation at specific sites using elastic net regression, a supervised machine learning method. The cortical clock was subsequently validated in a novel independent human cortex dataset (n = 1221, ages = 41 to 104 years) and tested for specificity in a large whole blood dataset (n = 1175, ages = 28 to 98 years). We identified a set of 347 DNA methylation sites that, in combination, optimally predict age in the human cortex. The sum of DNA methylation levels at these sites weighted by their regression coefficients provide the cortical DNA methylation clock age estimate. The novel clock dramatically outperformed previously reported clocks in additional cortical datasets. Our findings suggest that previous associations between predicted DNA methylation age and neurodegenerative phenotypes might represent false positives resulting from clocks not robustly calibrated to the tissue being tested and for phenotypes that become manifest in older ages. The age distribution and tissue type of samples included in training datasets need to be considered when building and applying epigenetic clock algorithms to human epidemiological or disease cohorts.

scholarly journals 821Surrounding greenness is associated with slower biological ageing based on epigenetics

2021 ◽  
Vol 50 (Supplement_1) ◽  
Author(s):  
Rongbin Xu ◽  
Shuai Li ◽  
Shanshan Li ◽  
Michael Abramson ◽  
John Hopper ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Vegetation Index ◽  
Normalized Difference Vegetation Index ◽  
Biological Aging ◽  
Mixed Effect ◽  
Community Construction ◽  
Mixed Effect Models ◽  
Important Health ◽  
Dna Methylation Age ◽  
Important Health Issue

Abstract Background High surrounding greenness has many health benefits, but few studies have evaluated these from the perspective of epigenetics. Methods We derived Horvath’s DNA methylation age (DNAmAge), Hannum’s DNAmAge, PhenoAge, and GrimAge from DNA methylation data measured from peripheral blood samples of 479 Australian women in 130 families. The DNA methylation age acceleration (DNAmAgeAC) was calculated as the residuals after regressing DNAmAge on chronological age. Greenness was represented by the satellite-derived Normalized Difference Vegetation Index (NDVI) and Enhanced Vegetation Index (EVI) within 300m, 500m, 1000m and 2000m surrounding participants’ home addresses. The greenness-DNAmAgeAC association was evaluated using a within-sibship design fitted by linear mixed effect models, adjusting for familial clustering and important covariates. Results Our analyses based on the whole sample suggested that the greenness-DNAmAgeAC association was only statistically significant for GrimAge acceleration. Each inter-quartile range (IQR) increase in NDVI within 1000m was associated with 0.59 (95% CI: 0.18, 1.01) year decrease in GrimAge acceleration. Greenness was also inversely associated with GrimAge’s three DNA methylation based components (cystatin-C, growth differentiation factor 15, and smoking pack-years). For participants at higher 50% area-level socioeconomic status (SES), each IQR increase in NDVI within 1000m was associated with 1.24 (95%CI: 0.39, 2.09) year and 0.79 (95%CI: 0.29, 1.30) year decrease in Hannum’s DNAmAgeAC and GrimAge acceleration, respectively. Conclusions Higher surrounding greenness was associated with slower biological aging measured by GrimAge acceleration and Hannun’s DNAmAgeAC in Australian women, particularly among those who lived in areas at higher SES. Key messages Epigenetics provides a potential mechanism for why surrounding greenness is an important health issue for community construction.

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